Enhancement of proton conductance by mutations of the selectivity filter of aquaporin-1

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Standard

Enhancement of proton conductance by mutations of the selectivity filter of aquaporin-1. / Li, Hui; Chen, Hanning; Steinbronn, Christina; Wu, Binghua; Beitz, Eric; Zeuthen, Thomas; Voth, Gregory A.

I: Journal of Molecular Biology, Bind 407, Nr. 4, 08.04.2011, s. 607-20.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Li, H, Chen, H, Steinbronn, C, Wu, B, Beitz, E, Zeuthen, T & Voth, GA 2011, 'Enhancement of proton conductance by mutations of the selectivity filter of aquaporin-1', Journal of Molecular Biology, bind 407, nr. 4, s. 607-20. https://doi.org/10.1016/j.jmb.2011.01.036

APA

Li, H., Chen, H., Steinbronn, C., Wu, B., Beitz, E., Zeuthen, T., & Voth, G. A. (2011). Enhancement of proton conductance by mutations of the selectivity filter of aquaporin-1. Journal of Molecular Biology, 407(4), 607-20. https://doi.org/10.1016/j.jmb.2011.01.036

Vancouver

Li H, Chen H, Steinbronn C, Wu B, Beitz E, Zeuthen T o.a. Enhancement of proton conductance by mutations of the selectivity filter of aquaporin-1. Journal of Molecular Biology. 2011 apr. 8;407(4):607-20. https://doi.org/10.1016/j.jmb.2011.01.036

Author

Li, Hui ; Chen, Hanning ; Steinbronn, Christina ; Wu, Binghua ; Beitz, Eric ; Zeuthen, Thomas ; Voth, Gregory A. / Enhancement of proton conductance by mutations of the selectivity filter of aquaporin-1. I: Journal of Molecular Biology. 2011 ; Bind 407, Nr. 4. s. 607-20.

Bibtex

@article{e88bbc0a0c6d4004a65c83da342d7246,

title = "Enhancement of proton conductance by mutations of the selectivity filter of aquaporin-1",

abstract = "Prevention of cation permeation in wild-type aquaporin-1 (AQP1) is believed to be associated with the Asn-Pro-Ala (NPA) region and the aromatic/arginine selectivity filter (SF) domain. Previous work has suggested that the NPA region helps to impede proton permeation due to the protein backbone collective macrodipoles that create an environment favoring a directionally discontinuous channel hydrogen-bonded water chain and a large electrostatic barrier. The SF domain contributes to the proton permeation barrier by a spatial restriction mechanism and direct electrostatic interactions. To further explore these various effects, the free-energy barriers and the maximum cation conductance for the permeation of various cations through the AQP1-R195V and AQP1-R195S mutants are predicted computationally. The cations studied included the hydrated excess proton that utilizes the Grotthuss shuttling mechanism, a model {"}classical{"} charge localized hydronium cation that exhibits no Grotthuss shuttling, and a sodium cation. The hydrated excess proton was simulated using a specialized multi-state molecular dynamics method including a proper physical treatment of the proton shuttling and charge defect delocalization. Both AQP1 mutants exhibit a surprising cooperative effect leading to a reduction in the free-energy barrier for proton permeation around the NPA region due to altered water configurations in the SF region, with AQP1-R195S having a higher conductance than AQP1-R195V. The theoretical predictions are experimentally confirmed in wild-type AQP1 and the mutants expressed in Xenopus oocytes. The combined results suggest that the SF domain is a specialized structure that has evolved to impede proton permeation in aquaporins.",

keywords = "Animals, Aquaporin 1, Cations, Cloning, Molecular, Computational Biology, Computer Simulation, Gene Expression, Models, Molecular, Mutant Proteins, Mutation, Missense, Oocytes, Protein Structure, Tertiary, Protons, Static Electricity, Xenopus",

author = "Hui Li and Hanning Chen and Christina Steinbronn and Binghua Wu and Eric Beitz and Thomas Zeuthen and Voth, {Gregory A}",

year = "2011",

month = apr,

day = "8",

doi = "10.1016/j.jmb.2011.01.036",

language = "English",

volume = "407",

pages = "607--20",

journal = "Journal of Molecular Biology",

issn = "0022-2836",

publisher = "Academic Press",

number = "4",

}

RIS

TY - JOUR

T1 - Enhancement of proton conductance by mutations of the selectivity filter of aquaporin-1

AU - Li, Hui

AU - Chen, Hanning

AU - Steinbronn, Christina

AU - Wu, Binghua

AU - Beitz, Eric

AU - Zeuthen, Thomas

AU - Voth, Gregory A

PY - 2011/4/8

Y1 - 2011/4/8

N2 - Prevention of cation permeation in wild-type aquaporin-1 (AQP1) is believed to be associated with the Asn-Pro-Ala (NPA) region and the aromatic/arginine selectivity filter (SF) domain. Previous work has suggested that the NPA region helps to impede proton permeation due to the protein backbone collective macrodipoles that create an environment favoring a directionally discontinuous channel hydrogen-bonded water chain and a large electrostatic barrier. The SF domain contributes to the proton permeation barrier by a spatial restriction mechanism and direct electrostatic interactions. To further explore these various effects, the free-energy barriers and the maximum cation conductance for the permeation of various cations through the AQP1-R195V and AQP1-R195S mutants are predicted computationally. The cations studied included the hydrated excess proton that utilizes the Grotthuss shuttling mechanism, a model "classical" charge localized hydronium cation that exhibits no Grotthuss shuttling, and a sodium cation. The hydrated excess proton was simulated using a specialized multi-state molecular dynamics method including a proper physical treatment of the proton shuttling and charge defect delocalization. Both AQP1 mutants exhibit a surprising cooperative effect leading to a reduction in the free-energy barrier for proton permeation around the NPA region due to altered water configurations in the SF region, with AQP1-R195S having a higher conductance than AQP1-R195V. The theoretical predictions are experimentally confirmed in wild-type AQP1 and the mutants expressed in Xenopus oocytes. The combined results suggest that the SF domain is a specialized structure that has evolved to impede proton permeation in aquaporins.

AB - Prevention of cation permeation in wild-type aquaporin-1 (AQP1) is believed to be associated with the Asn-Pro-Ala (NPA) region and the aromatic/arginine selectivity filter (SF) domain. Previous work has suggested that the NPA region helps to impede proton permeation due to the protein backbone collective macrodipoles that create an environment favoring a directionally discontinuous channel hydrogen-bonded water chain and a large electrostatic barrier. The SF domain contributes to the proton permeation barrier by a spatial restriction mechanism and direct electrostatic interactions. To further explore these various effects, the free-energy barriers and the maximum cation conductance for the permeation of various cations through the AQP1-R195V and AQP1-R195S mutants are predicted computationally. The cations studied included the hydrated excess proton that utilizes the Grotthuss shuttling mechanism, a model "classical" charge localized hydronium cation that exhibits no Grotthuss shuttling, and a sodium cation. The hydrated excess proton was simulated using a specialized multi-state molecular dynamics method including a proper physical treatment of the proton shuttling and charge defect delocalization. Both AQP1 mutants exhibit a surprising cooperative effect leading to a reduction in the free-energy barrier for proton permeation around the NPA region due to altered water configurations in the SF region, with AQP1-R195S having a higher conductance than AQP1-R195V. The theoretical predictions are experimentally confirmed in wild-type AQP1 and the mutants expressed in Xenopus oocytes. The combined results suggest that the SF domain is a specialized structure that has evolved to impede proton permeation in aquaporins.

KW - Animals

KW - Aquaporin 1

KW - Cations

KW - Cloning, Molecular

KW - Computational Biology

KW - Computer Simulation

KW - Gene Expression

KW - Models, Molecular

KW - Mutant Proteins

KW - Mutation, Missense

KW - Oocytes

KW - Protein Structure, Tertiary

KW - Protons

KW - Static Electricity

KW - Xenopus

U2 - 10.1016/j.jmb.2011.01.036

DO - 10.1016/j.jmb.2011.01.036

M3 - Journal article

C2 - 21277313

VL - 407

SP - 607

EP - 620

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 4

ER -

ID: 33543906

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